Emerging Multiscale Biofabrication Approaches for Bacteriotherapy.

Bacteriotherapy is emerging as a strategic and effective approach to treat infections by providing putatively harmless bacteria (i.e., probiotics) as antagonists to pathogens. Proper delivery of probiotics or their metabolites (i.e., post-biotics) can facilitate their availing of biomaterial encapsulation via innovative manufacturing technologies. This review paper aims to provide the most recent biomaterial-assisted strategies proposed to treat infections or dysbiosis using bacteriotherapy. We revised the encapsulation processes across multiscale biomaterial approaches, which could be ideal for targeting different tissues and suit diverse therapeutic opportunities. Hydrogels, and specifically polysaccharides, are the focus of this review, as they have been reported to better sustain the vitality of the live cells incorporated. Specifically, the approaches used for fabricating hydrogel-based devices with increasing dimensionality (D)-namely, 0D (i.e., particles), 1D (i.e., fibers), 2D (i.e., fiber meshes), and 3D (i.e., scaffolds)-endowed with probiotics, were detailed by describing their advantages and challenges, along with a future overlook in the field. Electrospinning, electrospray, and 3D bioprinting were investigated as new biofabrication methods for probiotic encapsulation within multidimensional matrices. Finally, examples of biomaterial-based systems for cell and possibly post-biotic release were reported.

Assessment of Electrospun Poly(ε-caprolactone) and Poly(lactic acid) Fiber Scaffolds to Generate 3D In Vitro Models of Colorectal Adenocarcinoma: A Preliminary Study.

Three-dimensional scaffold-based culture has been increasingly gaining influence in oncology as a therapeutic strategy for tumors with a high relapse percentage. This study aims to evaluate electrospun poly(ε-caprolactone) (PCL) and poly(lactic acid) (PLA) scaffolds to create a 3D model of colorectal adenocarcinoma. Specifically, the physico-mechanical and morphological properties of PCL and PLA electrospun fiber meshes collected at different drum velocities, i.e., 500 rpm, 1000 rpm and 2500 rpm, were assessed. Fiber size, mesh porosity, pore size distribution, water contact angle and tensile mechanical properties were investigated. Caco-2 cells were cultured on the produced PCL and PLA scaffolds for 7 days, demonstrating good cell viability and metabolic activity in all the scaffolds. A cross-analysis of the cell-scaffold interactions with morphological, mechanical and surface characterizations of the different electrospun fiber meshes was carried out, showing an opposite trend of cell metabolic activity in PLA and PCL scaffolds regardless of the fiber alignment, which increased in PLA and decreased in PCL. The best samples for Caco-2 cell culture were PCL500 (randomly oriented fibers) and PLA2500 (aligned fibers). Caco-2 cells had the highest metabolic activity in these scaffolds, with Young's moduli in the range of 8.6-21.9 MPa. PCL500 showed Young's modulus and strain at break close to those of the large intestine. Advancements in 3D in vitro models of colorectal adenocarcinoma could move forward the development of therapies for this cancer.

Placental growth factor as a predictive marker of preeclampsia - PREBIO study - PREeclampsia BIOchemical study.

INTRODUCTION: To evaluate the clinical utility of placental growth factor (PlGF) for the prediction of preeclampsia (PE). MATERIALS AND METHODS: This prospective cohort study included women divided into three groups: (1) pregnancies without preconceptional risk of developing PE; (2) pregnancies with a preconceptional and/or current risk of developing PE; (3) PE-complicated pregnancies (control group). Blood samples were collected every 4-5 weeks or during hospitalization from early second trimester until delivery in the group 1 and 2, at the diagnosis of PE in the group 3. Plasma levels of PlGF were measured using The Triage PlGF test (Alere) and considered pathological under the 5th centile for gestational age. Sensitivity (Sn), specificity (Sp), positive and negative predictive value (PPV, NPV) were calculated. RESULTS: In group 1, 30% of women (3/10) had pathological test but none of them developed PE (Sp 70%, NPV 100%). In group 2 (n = 75), none of the patients with normal test developed PE (0/24), while 39% of women with PlGF < 5th centile (20/51) developed PE (Sn 100%, Sp 44%, PPV 39%, NPV 100%). In group 3 (n = 11) all women except one had a pathological PlGF test (Sn 90%, PPV 100%). CONCLUSIONS: Our data support recent studies which identify PlGF as a biochemical marker not only of PE, but also of placental dysfunction. In fact, it is useful for ruling out PE in women at risk because of the high Sn and high NPV: a normal PlGF is related with a positive pregnancy outcome. Therefore, the measurement of this biomarker would simplify PE clinical management and would reduce costs.

Management of pregnancy blood pressure increase in the emergency room: role of PlGF-based biochemical markers and relative economic impact.

INTRODUCTION: To evaluate the clinical and economic impact of healthcare management of pregnant women with blood pressure increase (BPI) accessing emergency room (ER) and the utility of the introduction of a PlGF-based test in clinical practice. MATERIALS AND METHODS: This retrospective cohort study included women with single pregnancies who performed at least 1 ER access for BPI after the 20th gestational week in 2016. BPI was subsequently classified as significant if associated with preeclampsia (PE) or Fetal Growth Restriction (FGR) and not significant otherwise. Two experts evaluated potential changes in patients' management with the introduction of a PlGF-based test. The direct healthcare cost was estimated. RESULTS: We enrolled 107 patients, of which 30% showed significant BPI (17 PE cases, 13 FGR, and 2 both pathologies). Anamnestic, clinical, and laboratory evaluations were not effective in differentiating between significant and not significant BPI (p-values: .8320, .2856, and .2297, respectively). The introduction of a PlGF-based test would have reduced overtreatment and undertreatment. The test would have avoided 18% of all hospitalizations, 35% of hospitalizations for BPI, 43% of outpatient referrals, and 13% of ER accesses. The number of avoidable accesses was higher in women with not significant BPI. Overall, the mean total cost (from first ER access until delivery) was €2634 per woman and €401 would have been avoidable. CONCLUSION: The clinical integration of PlGF-based tests is advantageous in diagnostic, prognostic and economic terms, as an objective marker of placental dysfunction.